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In enzymology, an alanine racemase () is an enzyme that catalyzes the chemical reaction :L-alanine D-alanine Hence, this enzyme has one substrate, L-alanine, and one product, D-alanine. This enzyme belongs to the family of isomerases, specifically those racemases and epimerases acting on amino acids and derivatives. The systematic name of this enzyme class is alanine racemase. This enzyme is also called L-alanine racemase. This enzyme participates in alanine and aspartate metabolism and D-alanine metabolism. It employs one cofactor, pyridoxal phosphate. At least two compounds, 3-Fluoro-D-alanine and D-Cycloserine are known to inhibit this enzyme. The D-alanine produced by alanine racemase is used for peptidoglycan biosynthesis. Peptidoglycan is found in the cell walls of all bacteria, including many which are harmful to humans. The enzyme is absent in higher eukaryotes but found everywhere in prokaryotes, making alanine racemase a great target for antimicrobial drug development.〔Milligan, Daniel L., et al. (2007) The Alanine Racemase of Mycobacterium smegmatis Is Essential for Growth in the Absence of D-Alanine. Journal of Bacteriology 189, 8381-8386.〕 Alanine racemase can be found in some invertebrates. Bacteria can have one (alr gene) or two alanine racemase genes. Bacterial species with two genes for alanine racemase have one that is continually expressed and one that is inducible, which makes it difficult to target both genes for drug studies. However, knockout studies have shown that without the alr gene being expressed, the bacteria would need an external source of D-alanine in order to survive. Therefore, the alr gene is a feasible target for antimicrobial drugs.〔 ==Structural studies== To catalyze the interconversion of D and L alanine, Alanine racemase must position residues capable of exchanging protons on either side of the alpha carbon of alanine. Structural studies of enzyme-inhibitor complexes suggest that Tyrosine 25 and Lysine 39 are these residues. The alpha-proton of the L-enantiomer is oriented toward Tyr265 and the alpha proton of the D-enantiomer is oriented toward Lys39 (Figure 1). The distance between the enzyme residues and the enantiomers is 3.5A and 3.6A respectively.〔Watanabe, A., Yoshimura, T., Mikami, B., Hayashi, H., Kagamiyama, H., Esaki, N. (2002) Reaction Mechanism of Alanine Racemase from Bacillus stearothermophilus: X-ray crystallographic studies of the enzyme bound within -(5’-phosphopyridoxyl)alanine Journal of Biological Chemistry 277, 19166-19172.〕 Structural studies of enzyme complexes with a synthetic L-alanine analog, a tight binding inhibitor 〔Stamper, G. F., Morollo, A. A., and Ringe, D. (1998) Biochemistry 37, 10438 –10445〕 and propionate 〔Morollo, A. A., Petsko, G. A., and Ringe, D. (1999) Biochemistry 38, 3293–3301〕 further validate that Tyr265 and Lys39 are catalytic bases for the reaction,.〔〔Shaw, J. P., Petsko, G. A., and Ringe, D. (1997) Determination of the Structure of Alanine racemase from Bacillus stearothermophilus at 1.9-A Resolution Biochemistry 36, 1329–1342〕 The PLP-L-Ala and PLP-D-Ala complexes are almost superimposability.〔 The regions that do not overlap are the arms connected the pyridine ring of PLP and the alpha carbon of alanine. An interaction between both the phosphate oxygen and pyridine nitrogen atoms to the 5’phosphopyridoxyl region of PLP-Ala probably creates tight binding to the enzyme.〔 The structure of alanine racemase from ''Bacillus stearothermophilus'' (Geobacillus stearothermophilus) was determined by X-ray crystallography to a resolution of 1.9 A.〔Shaw, J. P., Petsko, G. A., and Ringe, D. (1997) Determination of the Structure of Alanine racemase from Bacillus stearothermophilus at 1.9-A Resolution Biochemistry 36, 1329–1342〕 The alanine racemase monomer is composed of two domains, an eight-stranded alpha/beta barrel at the N terminus, and a C-terminal domain essentially composed of beta-strand. A model of the two domain structure is shown in Figure 2. The N-terminal domain is also found in the PROSC (proline synthetase co-transcribed bacterial homolog) family of proteins, which are not known to have alanine racemase activity. The pyridoxal 5'-phosphate (PLP) cofactor lies in and above the mouth of the alpha/beta barrel and is covalently linked via an aldimine linkage to a lysine residue, which is at the C terminus of the first beta-strand of the alpha/beta barrel. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Alanine racemase」の詳細全文を読む スポンサード リンク
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